Ultrasonic characterization of ultrasound contrast agents

The main constituent of an ultrasound contrast agent (UCA) is gas-filled microbubbles. An average UCA contains billions per ml. These microbubbles are excellent ultrasound scatterers due to their high compressibility. In an ultrasound field they act as resonant systems, resulting in harmonic energy in the backscattered ultrasound signal, such as energy at the subharmonic, ultraharmonic and higher harmonic frequencies. This harmonic energy is exploited for contrast enhanced imaging to discriminate the contrast agent from surrounding tissue. The amount of harmonic energy that the contrast agent bubbles generate depends on the bubble characteristics in combination with the ultrasound field applied. This paper summarizes different strategies to characterize the UCAs. These strategies can be divided into acoustic and optical methods, which focus on the linear or nonlinear responses of the contrast agent bubbles. In addition, the characteristics of individual bubbles can be determined or the bubbles can be examined when they are part of a population. Recently, especially optical methods have proven their value to study individual bubbles. This paper concludes by showing some examples of optically observed typical behavior of contrast bubbles in ultrasound fields

Molecular imaging of inflammation and intraplaque vasa vasorum: A step forward to identification of vulnerable plaques?

Current developments in cardiovascular biology and imaging enable the noninvasive molecular evaluation of atherosclerotic vascular disease. Intraplaque neovascularization sprouting from the adventitial vasa vasorum has been identified as an independent predictor of intraplaque hemorrhage and plaque rupture. These intraplaque vasa vasorum result from angiogenesis, most likely under influence of hypoxic and inflammatory stimuli. Several molecular imaging techniques are currently available. Most experience has been obtained with molecular imaging using positron emission tomography and single photon emission computed tomography. Recently, the development of targeted contrast agents has allowed molecular imaging with magnetic resonance imaging, ultrasound and computed tomography. The present review discusses the use of these molecular imaging techniques to identify inflammation and intraplaque vasa vasorum to identify vulnerable atherosclerotic plaques at risk of rupture and thrombosis. The available literature on molecular imaging techniques and molecular targets associated with inflammation and angiogenesis is discussed, and the clinical applications of molecular cardiovascular imaging and the use of molecular techniques for local drug delivery are addressed

What scans we will read: imaging instrumentation trends in clinical oncology

Oncological diseases account for a significant portion of the burden on public healthcare systems with associated costs driven primarily by complex and long-lasting therapies. Through the visualization of patient-specific morphology and functional-molecular pathways, cancerous tissue can be detected and characterized non- invasively, so as to provide referring oncologists with essential information to support therapy management decisions. Following the onset of stand-alone anatomical and functional imaging, we witness a push towards integrating molecular image information through various methods, including anato-metabolic imaging (e.g., PET/ CT), advanced MRI, optical or ultrasound imaging. This perspective paper highlights a number of key technological and methodological advances in imaging instrumentation related to anatomical, functional, molecular medicine and hybrid imaging, that is understood as the hardware-based combination of complementary anatomical and molecular imaging. These include novel detector technologies for ionizing radiation used in CT and nuclear medicine imaging, and novel system developments in MRI and optical as well as opto-acoustic imaging. We will also highlight new data processing methods for improved non-invasive tissue characterization. Following a general introduction to the role of imaging in oncology patient management we introduce imaging methods with well-defined clinical applications and potential for clinical translation. For each modality, we report first on the status quo and point to perceived technological and methodological advances in a subsequent status go section. Considering the breadth and dynamics of these developments, this perspective ends with a critical reflection on where the authors, with the majority of them being imaging experts with a background in physics and engineering, believe imaging methods will be in a few years from now. Overall, methodological and technological medical imaging advances are geared towards increased image contrast, the derivation of reproducible quantitative parameters, an increase in volume sensitivity and a reduction in overall examination time. To ensure full translation to the clinic, this progress in technologies and instrumentation is complemented by progress in relevant acquisition and image-processing protocols and improved data analysis. To this end, we should accept diagnostic images as “data”, and – through the wider adoption of advanced analysis, including machine learning approaches and a “big data” concept – move to the next stage of non-invasive tumor phenotyping. The scans we will be reading in 10 years from now will likely be composed of highly diverse multi- dimensional data from multiple sources, which mandate the use of advanced and interactive visualization and analysis platforms powered by Artificial Intelligence (AI) for real-time data handling by cross-specialty clinical experts with a domain knowledge that will need to go beyond that of plain imaging

Biogenic gas nanostructures as ultrasonic molecular reporters

Ultrasound is among the most widely used non-invasive imaging modalities in biomedicine, but plays a surprisingly small role in molecular imaging due to a lack of suitable molecular reporters on the nanoscale. Here, we introduce a new class of reporters for ultrasound based on genetically encoded gas nanostructures from microorganisms, including bacteria and archaea. Gas vesicles are gas-filled protein-shelled compartments with typical widths of 45–250 nm and lengths of 100–600 nm that exclude water and are permeable to gas. We show that gas vesicles produce stable ultrasound contrast that is readily detected in vitro and in vivo, that their genetically encoded physical properties enable multiple modes of imaging, and that contrast enhancement through aggregation permits their use as molecular biosensors

Improved coalescence stability of monodisperse phospholipid-coated microbubbles formed by flow-focusing at elevated temperatures

Monodisperse phospholipid-coated ultrasound contrast agent (UCA) microbubbles can be directly synthesized in a lab-on-a-chip flow-focusing device. However, high total lipid concentrations are required to minimize on-chip bubble coalescence. Here, we characterize the coalescence probability and the long-term size stability of microbubbles formed using DPPC and DSPC based lipid mixtures as a function of temperature. We show that the coalescence probability can be dramatically reduced by increasing the temperature during bubble formation. Moreover, it is shown that the increased coalescence stability can be explained from an exponential increase of the relative viscosity in the thin liquid film between the colliding bubbles. Furthermore, it was found that the relative viscosity of a DPPC lipid mixture is 7.6 times higher than that of a DSPC mixture and that it can be explained solely from the higher DPPC liposome concentration. Regarding long-term bubble stability, the ratio of the initial on-chip bubble size to the final stable bubble size was always found to be 2.2 for DPPC and DSPC coated bubbles with 10 mol% DPPE-PEG5000, independent of the temperature. Moreover, it was demonstrated that the microbubble suspensions formed at elevated temperatures are highly stable over a time window of 2 to 4 days when collected in a vial. All in all, this work shows that, by increasing the temperature during bubble formation from room temperature to 70 °C, the efficiency of the use of phospholipids in microbubble formation by flow-focusing can be increased by 5 times